Evaluation of structural and biologic parameters of canine breast cancer support the suitability of the dog as a model for human breast cancer. Well characterized malignant and benign breast tissues were collected from 175 mastectomized dogs, and the clinical and morphologic data recorded. Histopathologic classification of canine breast tumor shows similiarities to human breast lesions with respect to (a) distribution of diagnostic categories (normotypic, pre-cancerous, in situ and invasive malignant lesions), (b) nuclear differentiation of malignant lesions, and (c) morphologic evidence of host-tumor immune reactivity. Clinical follow-up data indicate prognostic relevance of the classification system. For the evaluation of immunologic parameters of canine breast cancer, skin tests and direct leukocyte migration tests (LMT) were used as assays of breast cancer specific cell-mediated immunity (CMI). 41 breast cancer and 20 control dogs were tested against autologous, homologous, and human breast cancer and control tissues, and against gp 55, the major envelope glycoprotein of RIII-MuMTV. 6 of 20 canine and 2 of 4 human breast cancer tissues were identified that elicited positive LMT responses in breast cancer dogs, but not in control dogs. Approximately one half of the breast cancer dogs yielded positive responses to gp 55, that were stronger and more consistent in repetitive LMT as compared to those in control dogs. Control dogs non-reactive to a panel of breast cancer tissues prior to immunization, were immunized to gp 55 to test cross reactivity between gp 55 and breast cancer tissues. Testing for cross reactivity will als be done following adoptive transfer of gp 55-specific CMI. Such information is pertinent to the development of immunoprophylaxis/therapy of breast cancer.